Familial Coagulation Factor V Deficiency Caused by a Novel 4 Base Pair Insertion in the Factor V Gene: Factor V Stanford
J. L. Zehnder, D. D. Hiraki, C. D. Jones, N. Gross, F. C. Grumet
From the Departments of Pathology and Medicine (Hematology), Stanford University School of Medicine, Stanford, CA, USA
An index patient with pseudohomozygosity for factor V Leiden was
identified. Each of his two children inherited a different paternal factor
V allele; a daughter was heterozygous for factor V Leiden, with
100% factor V activity, and a son was heterozygous for factor V deficiency,
with 50% factor V activity. Genomic DNA was obtained from
family members, and the 25 factor V exons and flanking intronic regions
were sequenced in the proband and confirmed in the children.
Within exon 13 of factor V, a 4 base insertion was found at NT 2856 in
the proband and son, but not the daughter. This mutation, here designated
factor V Stanford, results in a frameshift with loss of a thrombin
activation site (R1545V) and premature termination of translation at
amino acid 1560.